WO2019156238A1 - Injector and method of injecting solution containing live cells into injection target using said injector - Google Patents

Abstract

The purpose of the present invention is to provide an injector which, when a solution containing live cells has been injected in an injection target, has a high ratio of live cells that function in the injection target to the live cells injected, and a method of injecting a solution containing live cells into an injection target using said injector. This purpose is met by an injector which injects a solution containing live cells into the aforementioned injection target, without injecting from the injector body through a prescribed structure that has been inserted into the injection target; the injector is provided with a housing unit which houses the solution containing live cells, and a nozzle unit through which the solution containing live cells, which has been pressurized, flows, and which has a discharge port for discharging the solution into the injection target, wherein the injector satisfies a prescribed condition.

Description

Injector and method for injecting solution containing biomolecule into injection object using the same

The present invention relates to an injector and a method for injecting a solution containing a biomolecule to an injection target using the injector.

In addition to needled syringes that perform injection via an injection needle, needleless syringes that perform injection without going through an injection needle, injection needles that are used to inject a drug solution into a living body, etc. There are catheters with a drive source.
Among these, a needleless syringe may be configured to inject an injection component by applying pressure to a storage chamber in which an injection solution is stored by pressurized gas, a spring, or electromagnetic force. For example, a configuration is adopted in which a plurality of nozzle holes are formed inside the syringe body, and a piston that is driven at the time of injection is arranged corresponding to each nozzle hole (Patent Document 1). With this configuration, an injection solution is simultaneously ejected from a plurality of nozzle holes to achieve uniform injection into the subject. Then, a plasmid containing a luciferase gene is injected into a rat, and the cells can be transferred with high efficiency.
Moreover, there exists a form using a pressurized gas as an injection power source of the injection solution in a needleless syringe. For example, there is exemplified a pressurization form in which a large pressure is instantaneously applied at the initial stage of injection and then the applied pressure is gradually reduced over 40 to 50 msec (Patent Document 2).

However, when a solution containing biomolecules is injected into an injection target using an injector, the ratio of the biomolecules that function in the injection target to the injected biomolecules is increased. There have been no reports focusing on the injection conditions of solutions containing biomolecules.

JP 2004-358234 A US Patent Application Publication No. 2005/0010168

The present invention has been made under such circumstances, and when a solution containing a biomolecule is injected into the injection target, an injector with a large ratio of biomolecules that function in the injection target with respect to the injected biomolecule, Another object of the present invention is to provide a method for injecting a solution containing a biomolecule into an injection target using the injector.

As a result of intensive studies, the present inventors have determined that the biomolecule within a predetermined time from the injection start time of the solution containing the biomolecule ejected from the injector in an injector containing the solution containing the biomolecule. As a result of paying attention to the injection pressure rate, which is a change in the injection pressure per unit time of the solution containing, and the injection pressure of the solution containing the biomolecule within a predetermined time from the injection start time of the solution containing the biomolecule, The present inventors have found that the above-mentioned injector can solve the above-mentioned problems and completed the present invention. The present invention is as follows.

[1] A solution containing a biomolecule is injected from the injector body into the injection target without performing injection through the predetermined structure in a state where the predetermined structure is inserted into the injection target. An injector for storing a solution containing a biomolecule, and a nozzle unit having an injection port through which the pressurized solution containing the biomolecule flows and is injected to the injection target. An injection pressure rate which is a change in injection pressure per unit time of the solution containing the biomolecule from the injection start time of the solution containing the biomolecule to a time of 0.20 milliseconds is 7.0 × 10 ³ MPa / Injector, and the injection pressure of the solution containing the biomolecule from the injection start time of the solution containing the biomolecule to 4.0 milliseconds is less than 25 MPa.
[2] The injection pressure rate, which is a change in the injection pressure per unit time of the solution containing the biomolecule, from the injection start time of the solution containing the biomolecule to the time 0.20 milliseconds is 2.3 × 10 ^4. The injector according to [1], which is at least MPa / second.
[3] In the first decreasing region of the injection pressure of the solution containing the biomolecule, the injection pressure becomes a bottom value immediately after the first peak injection pressure from the time when the first peak injection pressure of the solution containing the biomolecule decreases. The injector according to [1] or [2], wherein the time until the arrival time is 6.0 milliseconds or less.
[4] A method of injecting a solution containing a biomolecule into an injection target using the injector according to any one of [1] to [3].

According to the present invention, when a solution containing a biomolecule is injected into an injection target, an injector having a large ratio of biomolecules that function in the injection target to the injected biomolecule, and injection using the injector A method of injecting a solution containing a biomolecule into a subject can be provided.

It is a figure which shows schematic structure of the injector which concerns on one embodiment of 1st invention of this invention. It is a graph which shows the time passage of the injection pressure of the filled water based on one embodiment of 1st invention of this invention. It is a graph which shows the time passage of the injection pressure of the filled water based on one embodiment of 1st invention of this invention. According to one embodiment of the second invention of the present invention, a value obtained by dividing the expression level (luminescence intensity) of the gene after injecting the plasmid DNA solution containing the gene into the rat by the injection amount of the plasmid DNA solution. It is a graph to show. According to one embodiment of the second invention of the present invention, a value obtained by dividing the expression level (luminescence intensity) of the gene after injecting the plasmid DNA solution containing the gene into the pig by the injection amount of the plasmid DNA solution. It is a graph to show.

The present invention includes an invention of an injector (first invention) and an invention of a method of injecting a solution containing a biomolecule into an injection target using the injector (second invention).

<First invention>
According to a first aspect of the present invention, there is provided a solution containing a biomolecule from an injector body without performing injection through the predetermined structure in a state where the predetermined structure is inserted into an injection target. An injector for injecting into an injection target, comprising: a container for storing a solution containing a biomolecule; and an injection port through which the pressurized solution containing the biomolecule flows and is injected into the injection target An injection pressure rate that is a change in the injection pressure per unit time of the solution containing a biomolecule from the injection start time of the solution containing the biomolecule to a time of 0.20 milliseconds. 0.0 × 10 ³ MPa / second or more, and the injection pressure of the solution containing the biomolecule from the injection start time of the solution containing the biomolecule to 4.0 milliseconds is less than 25 MPa. is there.

In the injector according to the first aspect of the present invention, the injection is a change in the injection pressure per unit time of the solution containing the biomolecule from the injection start time of the solution containing the biomolecule to the time 0.20 milliseconds. The pressure speed is 7.0 × 10 ³ MPa / second or more, and the injection pressure of the solution containing the biomolecule from the injection start time of the solution containing the biomolecule to 4.0 milliseconds is less than 25 MPa. Thus, when the solution containing the biomolecule is injected into the injection target, the ratio of the biomolecule that functions in the injection target to the injected biomolecule can be increased.
Specifically, the injection pressure rate of the solution containing the biomolecule from the injection start time of the solution containing the biomolecule to the time 0.20 milliseconds is 7.0 × 10 ³ MPa / second or more, The deformation of the injection target is expected to be greatly caused, and the injection pressure of the solution containing the biomolecule from the injection start time of the solution containing the biomolecule to 4.0 milliseconds is less than 25 MPa, It is expected not to damage the infusion subject excessively. As a result, when the solution containing the biomolecule is injected into the injection target, the ratio of the biomolecule that functions in the injection target to the injected biomolecule can be increased.

At this time, the injection pressure rate of the solution containing the biomolecule from the injection start time of the solution containing the biomolecule to the time 0.20 milliseconds is preferably 2.3 × 10 ⁴ MPa / second or more, more preferably 3.4 × ¹⁰ 4 MPa / sec or more, further preferably 6.8 × ¹⁰ 4 MPa / sec or more. Moreover, although an upper limit is not restrict | limited in particular, For example, 7.5 * 10 < ⁴ > MPa / second or less is mentioned.
In addition, the injection pressure of the solution containing the biomolecule from the start time of injection of the solution containing the biomolecule to 4.0 milliseconds is preferably 20 MPa or less, and is usually higher than 0 MPa, and the living body is injected into the injection target. Since it is expected to be a sufficient output for delivering a solution containing molecules, it is preferably 1.5 MPa or more, more preferably 5.0 MPa or more, and even more preferably 7.0 MPa or more. More preferably, it is 15 MPa or more.

In addition, in the first decreasing region of the injection pressure of the solution containing the biomolecule, the injection pressure that reaches the bottom immediately after the first peak injection pressure is reached from the time when the first peak injection pressure of the solution containing the biomolecule starts to decrease. When the solution containing the biomolecule is injected into the injection target, the time to the time to perform is usually greater than 0 milliseconds and usually 6.0 milliseconds or less. The proportion of biomolecules that function in the injection target can be increased.
Here, the first peak injection pressure refers to the injection pressure at the earliest time among the times when the injection pressure of the solution containing biomolecules reaches the peak after the start of injection of the solution containing biomolecules. The first decreasing region of the injection pressure of the solution containing the biomolecule means that the injection pressure of the solution containing the biomolecule decreases from the first peak injection pressure and reaches a bottom value immediately after the first peak injection pressure. This refers to the area where the injection pressure drops.
Specifically, when the time is 6.0 milliseconds or less, it is expected that a solution containing a sufficient amount of biomolecules can be delivered without excessively penetrating the injection target due to a steep liquid flow. When the solution containing the biomolecule is injected into the injection target, the ratio of the biomolecule that functions in the injection target to the injected biomolecule can be increased.
At this time, the time is preferably 4.1 milliseconds or less, more preferably 1.0 milliseconds or less, further preferably 0.95 milliseconds or less, and 0.80 milliseconds. Or less, more preferably 0.40 milliseconds or less. Moreover, it is usually larger than 0 and preferably 0.30 milliseconds or longer.

In the first invention of the present invention, the biomolecule injected into the injection target is not particularly limited as long as it functions in the injection target when injected into the injection target. The biomolecule may be a natural product or may be artificially synthesized. For example, nucleic acid or derivative thereof; nucleoside, nucleotide, or derivative thereof; amino acid, peptide, protein, or derivative thereof; lipid or derivative thereof; metal ion; low molecular compound or derivative thereof; antibiotic; vitamin or derivative thereof Etc. As long as it is a nucleic acid, it may be DNA or RNA, and they may contain genes. In Examples described later, free plasmid DNA containing a luciferase gene is used as a biomolecule, and the luciferase gene is used as a reporter gene.
The biomolecule injected into the injection target is fixed to a carrier such as a nanoparticle in a free form as long as the biomolecule exists stably and there is no adverse effect such as destroying the injection target to be injected. The form may be sufficient and may be modified and the aspect is not specifically limited including a solvent.
When the DNA contains a gene, it may be designed in a form in which the gene is contained in an expression cassette or expression vector. Furthermore, for example, the gene may be placed under the control of a promoter suitable for the type of injection target into which DNA is injected and the injection site. That is, in any embodiment, a known genetic engineering technique can be used. In Examples described later, a mammalian expression vector pGL3 control vector (Promega) is used as an expression vector. Such plasmid vectors are known and can be obtained by those skilled in the art. Subcloning of expression vectors and recombinant vectors can be performed according to known methods.

(Function of biomolecule)
As an example of the ratio of the biomolecule that functions in the injection target to the biomolecule injected into the injection target being large, when the DNA as the biomolecule contains a gene, the amount of DNA injected into the injection target is The expression level of the gene is large. As the confirmation method, for example, after injecting a DNA solution into an injection target, a tissue is collected in a cylindrical shape having a desired radius around the DNA solution inlet, Samples can be prepared by biological methods and confirmed by an expression level assay of the gene. A known method can be used as appropriate depending on the type of the gene. For example, when the gene is a luciferase gene, an example of assaying the amount of luminescence using luciferin as a substrate can be given.

In the injector according to the first aspect of the present invention, the “front end side” means a side on which an injection port through which a solution containing a biomolecule is injected from the injector is disposed, Means the side opposite to the tip side of the injector, and these terms do not limit the specific location or position.

The injector according to the first aspect of the present invention provides a biomolecule from the injector body without performing injection through the predetermined structure in a state where the predetermined structure is inserted into the injection target. A solution containing the liquid is injected into the injection target. The injector according to the first aspect of the present invention is, for example, a device that guides a solution containing a biomolecule from the injector body to the injection target when the distance from the injector body to the injection target is large, for example, a catheter. A predetermined structure such as the above may be included. Therefore, the injector according to the first aspect of the present invention may or may not include such a predetermined structure. If the predetermined structure is included, the predetermined structure is injected. A solution containing a biomolecule inserted into the subject is not injected into the injection subject.

In the injector according to the first aspect of the present invention, the drive unit for pressurizing the solution containing the biomolecule is not particularly limited. The pressurization may be, for example, a pressure generated when the pressure of the compressed gas is released, or may be a pressure generated by combustion of explosives ignited by the ignition device. Further, pressurization using electromagnetic force, for example, pressurization by a linear electromagnetic actuator may be used. Preferably, at least the pressure generated by the combustion of the explosive ignited by the igniter is used, and may be used in combination with either one of the other two pressurization modes or both.
In the case of adopting an aspect using pressure generated by combustion of explosives ignited by an ignition device as pressurization, explosives include, for example, explosives (ZPP) containing zirconium and potassium perchlorate, titanium hydride and perchloric acid Gunpowder containing potassium (THPP), Gunpowder containing titanium and potassium perchlorate (TiPP), Gunpowder containing aluminum and potassium perchlorate (APP), Gunpowder containing aluminum and bismuth oxide (ABO), Aluminum and molybdenum oxide. It may be an explosive comprising any one of explosives containing (AMO), explosives containing aluminum and copper oxide (ACO), explosives containing aluminum and iron oxide (AFO), or a combination thereof. . As a feature of these explosives, even if the combustion product is a gas in a high temperature state, it does not contain a gas component at room temperature, so that the combustion product after ignition immediately condenses.
In addition, when the generated energy of the gas generating agent is used as the injection energy, the gas generating agent includes various gases used in single-base smokeless explosives, gas generators for airbags and gas generators for seat belt pretensioners. It is also possible to use a generator.

In the injector according to the first aspect of the present invention, the solution containing the biomolecule is not contained in the filling chamber from the beginning, but the solution containing the biomolecule is introduced into the filling chamber via the nozzle having the injection port. Accommodates by aspiration. Thus, by adopting a configuration that requires a filling operation into the filling chamber, it is possible to inject a solution containing any necessary biomolecules into the injection target. Therefore, in the injector according to the first aspect of the present invention, the syringe portion is configured to be detachable.

Hereinafter, a syringe 1 (needleless syringe) will be described as an example of an injector according to an embodiment of the first invention of the present invention with reference to the drawings. In addition, the structure of the following embodiment is an illustration and the 1st invention of this invention is not limited to the structure of this embodiment. Note that “front end side” and “proximal end side” are used as terms representing a relative positional relationship in the longitudinal direction of the syringe 1. The “front end side” represents a position closer to the distal end of the syringe 1, which will be described later, that is, a position closer to the injection port 31a. That is, the direction on the drive unit 7 side is shown. Further, this example is an example in which the combustion energy of the explosive ignited by the ignition device is used as the injection energy, and the DNA solution is used as the solution containing the biomolecule, but the first invention of the present invention is limited to this. Is not to be done.

(Configuration of syringe 1)
FIG. 1 is a diagram showing a schematic configuration of the syringe 1, and is also a cross-sectional view of the syringe 1 along its longitudinal direction. The syringe 1 includes a syringe assembly 10 in which a subassembly composed of a syringe part 3 and a plunger 4 and a subassembly composed of a syringe body 6, a piston 5, and a drive part 7 are assembled together. , And is configured by being attached to a housing (syringe housing) 2.

As described above, the syringe assembly 10 is configured to be detachable from the housing 2. The filling chamber 32 formed between the syringe part 3 and the plunger 4 included in the syringe assembly 10 is filled with the DNA solution, and the syringe assembly 10 is disposable every time the DNA solution is ejected. Is a unit. On the other hand, on the housing 2 side, a battery 9 for supplying electric power to an igniter 71 included in the drive unit 7 of the syringe assembly 10 is included. The power supply from the battery 9 is performed by the user pressing the button 8 provided on the housing 2, so that the electrode on the housing 2 side and the electrode on the drive unit 7 side of the syringe assembly 10 are connected via the wiring. Will be done between. The electrode on the housing 2 side and the electrode on the drive unit 7 side of the syringe assembly 10 are designed so that the shape and position of both electrodes are automatically contacted when the syringe assembly 10 is attached to the housing 2. ing. Further, the housing 2 is a unit that can be used repeatedly as long as the electric power that can be supplied to the drive unit 7 remains in the battery 9. In the housing 2, when the power of the battery 9 is exhausted, only the battery 9 may be replaced and the housing 2 may continue to be used.

Further, in the syringe body 6 shown in FIG. 1, no additional explosive component is arranged, but in order to adjust the pressure transition applied to the injection solution via the piston 5, the explosive combustion in the igniter 71 is performed. A gas generating agent or the like that burns with the combustion products generated by the above to generate gas can be disposed in the igniter 71 or in the through hole of the syringe body 6. The configuration in which the gas generating agent is arranged in the igniter 71 is a known technique as disclosed in International Publication No. 01-031282, Japanese Patent Application Laid-Open No. 2003-25950, and the like. Moreover, as an example of the gas generating agent, a single base smokeless gunpowder composed of 98% by mass of nitrocellulose, 0.8% by mass of diphenylamine and 1.2% by mass of potassium sulfate can be mentioned. It is also possible to use various gas generating agents that are used in gas generators for airbags and gas generators for seat belt pretensioners. It is possible to change the combustion completion time of the gas generating agent by adjusting the size, size, and shape, particularly the surface shape of the gas generating agent when arranged in the through-hole. The pressure transition applied to the solution can be a desired transition, that is, a transition in which the DNA solution can be appropriately injected into the injection target. In the first invention of the present invention, it is assumed that the gas generating agent used as necessary is also included in the drive unit 7.

(Injection target)
The injection target in the first invention of the present invention may be any of a cell, a cell sheet, a tissue, an organ (organ), an organ system, an individual (living body), and the like, and is not limited. Moreover, about the upper hierarchy as said injection | pouring object, you may target the lower hierarchy contained in it. That is, for example, when a tissue is an injection target, a cell included in the tissue may be an injection target, an intercellular matrix included in the tissue may be an injection target, or both may be an injection target.
A preferable infusion target includes the infusion subject derived from mammals. More preferred is the skin of a mammal individual (living body), and still more preferred is one or more tissues selected from the group consisting of intradermal, subcutaneous and skin muscles in the skin. In this case, one or more tissues selected from the group consisting of intradermal, subcutaneous, and skin muscles in the skin are ejected from the injector onto the skin surface of a mammal individual (living body). The method of injecting can be adopted.
In addition, a system for injecting a solution containing a biomolecule from an injector into an injection target may be any of an in vitro system, an in vivo system, and an ex vivo system.
Moreover, although it does not restrict | limit especially as a mammal, A human, a mouse | mouth, a rat, a guinea pig, a hamster, a cow, a goat, a sheep, a pig, a monkey, a dog, a cat etc. are mentioned. Moreover, the aspect except a human is also mentioned as a mammal depending on injection object.

<Second invention>
A second invention of the present invention is a method for injecting a solution containing a biomolecule into an injection target using the injector of the first invention.
Regarding the injector, the injection target, and the solution containing the biomolecule in the second invention of the present invention, the above description of the first invention of the present invention is incorporated.

Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to the following examples without departing from the gist thereof.

(Evaluation of injector injection pressure)
[Example 1-1]
The injector (nozzle diameter: 0.1 mm diameter) shown in FIG. 1 was filled with 100 μL of water, and the injection pressure in the injector from the pressurization of water by the combustion of the igniting agent until after injection was evaluated. As the explosive, 55 mg of an explosive (ZPP) containing zirconium and potassium perchlorate was used, and 40 mg of a single base smokeless explosive (hereinafter sometimes referred to as “GG”) was used as a gas generating agent.
As for the measurement of the injection pressure, as in the measurement method described in JP-A-2005-21640, the injection force is distributed and applied to the diaphragm of the load cell arranged downstream of the nozzle, and the output from the load cell is Measured by a method in which the data is collected by the data collection display device through the detection amplifier and displayed and stored as the time-dependent power (N), and the power (N) is divided by the area of the nozzle opening. Calculated.
[Example 1-2]
The procedure was the same as Example 1-1 except that 35 mg of ZPP was used.
[Example 1-3]
Example 11 was repeated except that 15 mg of ZPP was used.
[Example 1-4]
Example 1-1 was repeated except that 25 mg of ZPP was used.

FIG. 2 is a graph showing the time course of water injection pressure in each example. FIG. 3 is an enlarged view of the initial 0.20 millisecond graph in FIG. Table 1 shows each parameter.

(Evaluation of gene expression using rats)
[Example 2-1]
The syringe used in Example 1-1 was filled with 30 μL of a plasmid pGL3-control vector (Promega) solution containing a luciferase gene (solvent: endotoxin-free TE buffer, final concentration: 1.0 mg / mL), It injected into the skin of the back of a female SD rat (10 weeks old).
Prepare a lysate prepared by diluting “Cell Culture Lysis × 5” of Luciferase assay system (Promega) 5 times and placing 1.5 mL in a 2 mL microtube. , Subcutaneous and cutaneous muscles) were cut to a size of about 1 cm square and added to the lysate. Using dissecting scissors, finely chop the tissue into fine particles of 2 mm square or less in the lysate (the scissors were moved about 100 minutes about 2 minutes). Stir with a vortex mixer or ultrasonic cleaner for 10 seconds. did. Next, the microtube was frozen at −80 ° C. or in a dry ice atmosphere for about 15 minutes. After confirming that it was frozen, it was left at room temperature for about 20 minutes and thawed. This freezing and thawing was repeated three times in total to promote cell destruction. Thereafter, the sample was centrifuged (temperature 4 ° C., rotation speed 2000 rpm, time 5 min), and a supernatant was obtained.
The luciferase assay was performed using Lumitester C100 (Kikkoman Biochemifa Co., Ltd.). First, Luciferase Assay Substrate of Luciferase assey system was returned to room temperature and opened, and 10 mL of Luciferase Assay Buffer returned to room temperature was added thereto. It was shaken lightly to avoid foaming, and it was confirmed that it was dissolved. 100 μL of this was added to the Lumi tube, and 20 μL of the serum sample to be measured was added. Within about 20 seconds, the sample was placed in the measurement room of the Lumitester and measured, and the emission intensity was obtained. The luminescence intensity correlates with the expression level of the luciferase gene.
[Example 2-2]
Example 2-1 was the same as Example 2-1 except that the injector used in Example 1-2 was used.
[Example 2-3]
Example 2-1 was the same as Example 2-1 except that the injector used in Example 1-3 was used.
[Example 2-4]
Example 2-1 was the same as Example 2-1 except that the injector used in Example 1-4 was used.

FIG. 4 is a graph showing the value obtained by dividing the expression level (luminescence intensity) of the luciferase gene by the plasmid DNA injection amount in each Example. The horizontal line in the graph indicates the average value.

(Evaluation of gene expression using pigs)
[Example 3-1]
The injector used in Example 1-1 was filled with 100 μL of a plasmid pGL3-control vector (Promega) solution containing a luciferase gene (solvent: endotoxin-free TE buffer, final concentration: 1 mg / mL) for female edible use. The procedure was the same as in Example 2-1, except that the skin was injected into the abdomen of a pig (3 months old, weighing approximately 65 kg), and after 24 hours of breeding, intradermal tissue was used as a sample for luciferase assay.

FIG. 5 is a graph showing the value obtained by dividing the expression level (luminescence intensity) of the luciferase gene by the plasmid DNA injection amount in Example 3-1. The horizontal line in the graph indicates the average value.

DESCRIPTION OF SYMBOLS 1 .... Syringe 2 .... Housing 3 .... Syringe part 4 .... Plunger 5 .... Piston 6 .... Syringe main body 7 .... Drive part 8 .... Button 9 ... Battery 10 ... Syringe assembly 31 ... Nozzle part 31a ... Injection port 32 ... Filling chamber 71 ... Igniter

Claims (4)

An injector for injecting a solution containing a biomolecule from an injector body into the injection target without performing injection through the predetermined structure in a state where the predetermined structure is inserted into the injection target. Because
A container for containing a solution containing a biomolecule;
A nozzle part having an injection port through which a pressurized solution containing the biomolecule flows and is injected into the injection target;
With
The injection pressure rate, which is a change in the injection pressure per unit time of the solution containing the biomolecule, from the injection start time of the solution containing the biomolecule to the time of 0.20 milliseconds is 7.0 × 10 ³ MPa / second. The injection pressure of the solution containing the biomolecule from the start time of injection of the solution containing the biomolecule to 4.0 milliseconds is less than 25 MPa.
Syringe. The injection pressure rate, which is a change in the injection pressure per unit time of the solution containing the biomolecule, from the injection start time of the solution containing the biomolecule to the time 0.20 milliseconds is 2.3 × 10 ⁴ MPa / second. That's it,
The injector of claim 1. In the first decreasing region of the injection pressure of the solution containing the biomolecule, the time when the injection pressure that reaches the bottom immediately after the first peak injection pressure is reached from the start time when the first peak injection pressure of the solution containing the biomolecule decreases The time until is 6.0 milliseconds or less,
The injector according to claim 1 or 2. A method for injecting a solution containing a biomolecule into an injection target using the injector according to any one of claims 1 to 3.

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